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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor
Javier Casas1, Joanna Brzostek1, Veronika I Zarnitsyna2
11] Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore [2] Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
None:
The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck.
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